The UK Prospective Diabetes Study is a long-term, prospective randomized trial of therapies of Type II diabetes, to determine whether (a) improved plasma glucose control (with either insulin or sulphonylurea) or (b) improved blood pressure control (with a beta-blocker or ACE inhibitor) will prevent either the macro- or microvascular complications of diabetes. The specific aims of this application are to assess prospectively biochemical variables which have been postulated to be related to the pathophysiology of macro- or microvascular complications, to determine whether (a) they provide useful clinical information to determine which patients are particularly at risk from complications (b) they respond to different therapies of blood glucose or hypertension (c) they provide data which will elucidate the pathophysiology of different macro- or microvascular complications. Preliminary analyses show that microalbuminurea, plasma N acetylglucosaminidase (NAGase) and plasma factor VIII related antigen were associated with glycemia and decreased during the initial 3 months' diet as the plasma glucose decreased. For example, the albumin/creatinine ratio reduced from geometric mean 0.92 to 0.64 g/nmol (p<0.0001) but over the next 3 years it increased to 1.11 g/nmol (p<0.001). At presentation it was more closely associated with glycemia than with hypertension, but subsequently the reverse occurred. The degree to which improved blood glucose control or improved blood pressure control will prevent deterioration of these biochemical variables will be a crucial analysis. Longer follow-up is needed to determine whether these variables are more valuable marks of subsequent Growth complications than the plasma glucose or blood pressure measurements.Growth hormone and urine NAGase assays are being done. The study has now recruited 4,600 patients and is planned to recruit 5,200 patients. Many macro- and microvascular clinical events are occurring and the Study provides a unique opportunity to study biochemical and clinical measurements which could be important to physicians in determining the appropriate therapy of patients.